Objective: This study aimed to examine the expression of M-CSF, TNF-β, IFN-γ, and IL-10 in rats with liver cirrhosis and hypersplenism, and to investigate its significance.Methods: Seventy-two healthy male SD rats were randomly divided into a model group (n=60) and a control group (n=12). The rats in the model group were first gavaged with a 40% CCL4/peanut oil solution to develop cirrhosis and hypersplenism. The expression rates and intensities of the pro-inflammatory cytokines M-CSF, TNF-β, and IFN-γ, and the anti-inflammatory cytokine IL-10 in the spleen were measured and compared with the control group. The pro-inflammatory/anti-inflammatory cytokine ratio and its role were analyzed. Results:The positive expression rates of M-CSF, TNF-β, IFN-γ, and IL-10 in the model group (cirrhosis and hypersplenism) were 61.76%, 79.41%, 64.70%, and 88.24%, respectively, which were significantly different (P<0.05) from the 25%, 33.33%, 16.67%, and 50% in the control group. The relative protein expression intensities of M-CSF, TNF-β, IFN-γ, and IL-10 in the model group were 0.63 ± 0.58, 1.06 ± 0.49, 0.99 ± 0.38, and 1.12 ± 0.42, respectively, and were significantly different (P<0.05) from the 0.18 ± 0.12, 0.52 ± 0.27, 0.38 ± 0.28, and 0.60 ± 0.32 in the control group. The relative mRNA expression levels of M-CSF, TNF-β, IFN-γ, and IL-10 in the model group were 2.06 ± 0.11, 4.07 ± 0.19, 2.98 ± 0.11, and 7.94 ± 0.27, respectively, and were significantly different (P<0.05) from the 1.01 ± 0.05, 1.06 ± 0.11, 1.00 ± 0.31, and 1.02 ± 0.08 in the control group. Conclusion:The abnormally increased expression of M-CSF, TNF-β, IFN-γ, and IL-10 in rats with liver cirrhosis and hypersplenism, as well as the abnormal pro-inflammatory/anti-inflammatory cytokine ratio and regulation may play an important role in enhancing the phagocytosis of macrophages and causing peripheral cytopenias.