Objective:To observe the effects of fluoxetine on the lipid metabolism in mouse liver and investigate the mechanisms. Methods:All mice received an intraperitoneal injection of saline (control),fluoxetine (10 mg/kg or 25 mg/kg) or clozapine (25 mg/kg). The mice were sacrificed at 6h or 24h after injection,and the livers were collected. Liver neutral lipid was determined by oil red O staining. Liver triglyceride and total cholesterol were measured by test kits. Liver sterol regulatory element-binding protein 1c (SREBP1c),acetyl-CoA carboxylase 1 (ACC1) and fatty acid synthase (FAS) as well as carboxylesterase 1 (CES1) and carboxylesterase 3 (CES3) protein levels were determined by Western Blot. Results:Acute fluoxetine treatment induced hepatic lipid accumulation in mouse liver. Furthermore,the expression of ACC1 and FAS was evidently elevated while the expression of triacylglycerol hydrolases,CES1 and CES3 was suppressed by fluoxetine. Meanwhile,the expression of SREBP1c,a lipid-modulating transcription factor,was also stimulated by fluoxetine. Conclusion:These data suggest that fluoxetine may upregulate lipogenesis via SREBP1c,as well as downregulate lipolysis in mouse liver,resulting in hepatic lipid accumulation.