Background Our previous in vitro study has shown that total flavonoids from the leaves of Carya cathayensis exert estrogenic activities by promoting the expressions of ERα and ERβ. C. cathayensis leaf extract (CCE) was rich in flavonoids. Oral administration of CCE reduced the serum lipids and hepatic lipids, alleviated liver steatosis in ovariectomized rats. Objective To investigate whether CCE has estrogenic effects on reproductive tissue and influences lipid metabolism in ovariectomized rats, and whether CCE has a direct effect on regulation of lipid synthesis and/or oxidation and adipocyte differentiation of ovariectomized (OVX) rats. Methods Female Sprague–Dawley rats were ovariectomized and treated with CCE or estradiol in combination with a normal diet (ND), a high-fat diet (HFD) for 8 weeks. Histological analysis of uterus were performed and the lipid metabolism-related enzyme activity were examined. Expression of liver lipogenesis-related genes, adipocyte differentiation- and fat accumulation-related genes and protein were measured. Rusults Ovariectomy accelerated the uterine atrophy, development of dyslipidemia and hepatic steatosis, which were effectively mitigated by CCE supplementation. CCE significantly elevated ovariectomy-induced reduction in the cross-section area of the uterus and uterine glands. Compared with the OVX group, CCE increased the activities of lipoprtein lipase (LPL) and hepatic lipase (HL), decreased the hepatic mRNA expressions of Fas, Srebf1, Sla2a2, and increased Ppar α expressions at the mRNA levels under both ND and HFD conditions. CCE also decreased the Pck1 and G6pc mRNA expressions under HFD conditions, and show no significant effects on Hmgcr. The expressions of SREBF1, CEBPA and VEGF at the protein level were effectively regulated by CCE supplementation. Conclusion CCE effectively alleviated ovariectomy-induced dyslipidemia and visceral fat accumulation by modulating hepatic lipogenesis and adipocyte differentiation. Furthermore, CCE exhibited estrogenic activity for the prevention of postmenopausal fatty liver.