Objective To assess the effects of splenectomy on CCl4-induced liver fibrosis in rats. Methods Wistar rats were injected with CCl4 subcutaneously for 3 to 15 weeks to develop liver fibrosis. Two hundred and thirty-six rats were divided into 9 groups: (1) model group without splenectomy; (2) splenectomized group in which operation was performed before induction of fibrosis; (3) sham-operated group in which caparotomy was done before induction of fibrosis; (4)(5)(6) groups in which splenectomy was performed at the 6th, 9th and 12th week after induction of fibrosis, respectively; and (7) (8) (9) sham operation was also performed at the 6th, 9th and 12th week after induction of fibrosis, respectively. The spleen and liver biopsy, hepatic hydroxyproline, liver homogenate levels of procollagen type Ⅲ (PC Ⅲ), hyaluronic acid (HA), laminin (LN) and volume density of collagen were examined at different times. Results The results showed that the degree of hepatic damage and liver fibrosis in splenectomized group was significantly milder than that in model group and sham-operated groups. Splenectomy might delay the progress of liver fibrosis for about 3 weeks. The role of preventing rat liver fibrosis was also observed when splenectomy was performed after CCl4 induction of fibrosis for 6 and 9 weeks. Conclusions These results suggest that splenectomy may be of a preventive role against CCl4-induced rat liver fibrosis to a certain degree.