Connective tissue growth factor, are widely regarded as universal mediators of fibrosis and organ remodeling. TGF-b1 has long been regarded as the most potent stimulator of collagen synthesis during lung fibrosis. Cell-based GSI-IX 208255-80-5 studies have shown that CTGF regulates multiple processes that contribute to lung fibrosis, and data from animal models of human disease also reported the importance of CTGF in fibrosis. However, the detailed correlation between obesity, airway inflammation and remodeling remains to be elucidated. The mechanistic basis of obesity and asthma has been thoroughly investigated by Shore and her colleagues through using several different mice models of obesity. In these studies, either genetic ob/ob, db/db, carboxypeptidase E-deficient mice or high fat diet induced obese mice exhibited innate AHR. Although ob/ob and db/db mice are extensively used for studies of obesity-related pathophysiology, mutations in the leptin gene or its receptor are rarely described in humans. In fact, high-fat diet induced obesity better resembles the development of human obesity. However, high-fat diet alters pulmonary responses to allergen, which makes it hard to distinguish the individual effects of obesity or high-fat diet while in study of increased asthmatic susceptibility in obese mice. Therefore, it is necessary to determine whether AHR occurs in other mice models of obesity. Previous studies showed that early neonatal overfeeding has significant impacts on the long-term regulation of body weight and contributes to the development of obesity in adulthood. One well-established model to study the effect of neonatal overfeeding is the manipulation of the size of mice litters at the early stage of life. When pups are raised in small litter, e.g. 3 pups/litter presumably milk intake in each individual pup is greater than its control that is raised in a normal sized litter with around 10 pups/litter. These chronic neonatal overfeeding mice are characterized by persistent overweight and early onset of obesity, hyperleptinemia, hyperinsulinemia, glucose intolerance, impaired hypothalamic feeding circuitry, impaired norepinephrine turnover and brown adipose tissue thermogenesis. In the present study, we investigate the short-term and long-term effects of neonatal overfeeding on pulmonary function and inflammation. In the current study, we observed that neonatal overfeeding induced by litter size reduction could enhance airway hyperresponsiveness and lung inflammation, both of which were reported in other genetic types of obese mice, such as ob/ob, Cpefat mice and high fat diet induced obese mice. These studies suggest that airway hyperresponsiveness and inflammation are common features of obese mice. In addition, our data indicated that mice must maintain obesity for an extended period of time before the airway hyperresponsiveness was observed. Furthermore, our current study provided additional evidence that obesity resultant from neonatal overfeeding exhibited significant airway remodeling, characterized by collagen accumulation. To our knowledge, this is the first study to assess the relationship between neonatal overfeeding, airway inflammation and remodeling. Rodent pups suckled in litters of varied sizes have been extensively used as experimental models in studying metabolic and behavior development. Taking them as experimental models, our present study confirmed previous findings and demonstrated that when ICR pups were raised in small litters with 3 pups per litter.