Tetrahydropalmatine (THP), one of the active components of Rhizoma corydalis, has been reported to exert several pharmacological effects, including anti‑inflammatory, anti‑tumor and analgesic activities. However, its effect on obesity and the underlying molecular mechanisms that may be involved have not yet been elucidated. In the present study, the inhibitory effects of THP on the adipogenesis in 3T3‑L1 adipocytes was examined using hstology, western blotting and RT‑qPCR. THP was identified to significantly suppress lipid accumulation in 3T3‑L1 cells and it inhibited pre‑adipocyte differentiation in a concentration‑dependent manner, as evidenced by the reduced formation of lipid droplets and decreased triglyceride levels and glycerol‑3‑phosphate dehydrogenase activity. THP downregulated the adipogenesis‑associated protein and gene expressions of sterol regulatory element‑binding protein 1, fatty acid synthase, stearoyl‑CoA desaturase 1, peroxisome proliferator activated receptor γ and CCAAT/enhancer binding protein‑α in a concentration‑dependent manner. In addition, it reduced adipocyte fatty acid binding protein and glycerol‑3‑phosphate acyltransferase gene expression in a concentration‑dependent manner. Conversely, THP increased the mRNA expression of carnitine palmitoyltransferase 1 in a concentration‑dependent manner. Furthermore, THP increased AMP‑activated protein kinase (AMPK) and acetyl‑CoA carboxylase phosphorylation in a concentration‑dependent manner. These results suggested that anti‑adipogenic activity of TPH may be mediated via the AMPK pathway in 3T3‑L1 cells.