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Objective To explore the influence of splenectomy on liver homing and treatment of cirrhosis after adipose tissue derived mesenchymal stem cells (ADSCs) infusion. Methods The rats liver cirrhosis model was established and randomly divided into four groups, sham operation group (sham), sham operation + ADSCs infusion group (ADSCs), splenectomy group (Sp), splenectomy + ADSCs infusion group (Sp+ADSCs). The cell infusion was performed one week after sham or splenectomy. Then, liver function, pathological and homing changes were detected one week later. Results The isolated ADSCs were CD29 positive and underwent adipogenic and chondrogenic differentiation, the hepatic fibrosis area in ADSCs group was significantly smaller than that sham operation group (P＜0.05), and the fibrotic area in Sp+ADSCs group reduced as compared with that ADSCs group(P＜0.05). The expression of collagen Ⅰ mRNA in ADSCs group was significantly decreased as compared with that in sham group(P＜0.05), and mRNA coding collagen Ⅰ in Sp+ADSCs group was further decreased as compared with that in ADSCs group. As compared with ADSCs group[ALT: (280±56)U/L], Sp+ADSCs group [ALT: (213±89)U/L] had a significant difference in inhibiting liver injury (P＜0.05); Ex vitro fluorescence imaging showed that the fluorescence signal intensity in liver tissue of the Sp+ADSCs was significantly higher than that in ADSCs group (P＜0.05). Conclusions Splenectomy can significantly improve the live homing of ADSCs and improve their therapeutic effect on liver cirrhosis.