Obesity is related to many chronic diseases, including type 2 diabetes, fatty liver, cardiac vascular disease, and cancers. Resveratrol (RSV, trans‐3, 4’, 5‐trihydroxystilbene), a phenolic compound, has been reported to have anti‐oxidation, anti‐inflammation, anti‐platelet aggregation, anti‐cancer, protecting against cardiac vascular disease, and promotion longevity. Recently, several researches pointed out that RSV can attenuate high‐fat‐diet (HFD) induced obesity; however, its underlying mechanisms are not fully elucidated. In the present study, the HFD‐fed mice and 3T3‐L1 preadipocytes were employed to further explore the anti‐obese mechanisms of RSV. The 10‐week‐old male C57BL/6C mice were fed with HFD and treated HFD mice with or without RSV (1, 3, 10, or 30 mg/kg) for 10 weeks simultaneously. In RSV‐treated groups, the body weight gain was reduced significantly compared to compared to chow diet fed mice, which demonstrated that RSV has anti‐obesity effect. In respect of in vitro study, RSV (10–100 μM) treatment significantly decreased cell viability and increased apoptosis in both 3T3‐L1 preadipocytes and differentiated adipocytes. RSV (3–10 μM) suppressed preadipocytes differentiation by decrease PPARγ and Perilipin proteins expressions. RSV (3 μM) also inhibited lipolysis in mature adipocyte. Taking together, these results indicate that RSV exerted anti‐obese effects may through inhibition of preadipocyte proliferation and differentiation. Moreover, the anti‐lipolysis of RSV may contribute to maintain the lipids storage function in matured adipocyte which might have potential to prevent ectopic lipid accumulation.