Objective To investigate the effect of follistatin-like protein 1 (FSTL1) on inflammation and brown adipose tissue (BAT) in high-fat diet induced obesity in C57BL/6 J mice. Methods C57BL/6 J mice were divided into two groups and every group contained eight mice. Mice at 6-week of age were fed with high fat diet (HFD) or regular diet (RD) for 12 weeks. The body weight of the mice was measured every week, and the food intake was also recorded. After 12 weeks, glucose tolerance test and insulin tolerance test were performed before sacrifice. Subcutaneous white adipose tissue (SWAT), perirenal white adipose tissue (PWAT), epididymis white adipose tissue (EWAT), and brown adipose tissue (BAT) were collected and weighed. HE staining was applied toobserve Crown-like structures (CLS) in SWAT, PWAT, EWAT and the change of BAT. RT-PCR was performed to evaluate the mRNA levels of tumor necrosis factor (TNF-α), interleukin(IL)-6, IL-10 and FSTL in EWAT. Western blotting was used to analyze the protein levels of uncoupling protein 1(UCP1) and FSTL1 in BAT.Results The data showed that body weight and fat weight were significantly increased in HFD mice compared to those in RD mice. Food intake were significantly decreased in HFD mice compared to that in RD mice. Impaired glucose tolerance and insulin tolerance were present in HFD mice. In addition, CLS were observed in EWAT, but not in SWAT and PWAT of HFD mice. The mRNA levels of TNF-α, IL-6 and IL-10 in EWAT from HFD mice were significantly increased compared to those from RD mice. Meanwhile, The mRNA levels of FSTL1 in EWAT from HFD mice were also significantly increased compared to that from RD mice. The data from Western blotting showed that both UCP1 and FSTL1 were significantly increased in BAT of HFD mice compared to those in RD mice. Conclusion The present data indicates that the increased expression of inflammation-related genes and function of BAT may be related to the high level of FSTL1 in HFD-induced obesity.