Objective To explore the amelioration effect of Cripto-1 on the immunosuppression of macrophage differentiation induced by allogeneic transfusion. Methods BALB/c and C57BL/6 mice were selected for allogeneic blood transfusion and their macrophages were cultured. A stable L02 cell line with Cripto-1 overexpression was established and co-cultured with macrophages. The protein expression and mRNA levels of anti-inflammatory cytokines IL-10 and pro-inflammatory cytokines (TNF necrosis factor α(TNF-α), IL-6, transforming growth factor β(TGF-β) and IL-1β) were detected by Elisa and RT-PCR. The expression of NF-kB pathway protein was detected by western blot. Results Blot detection of Cripto-1 was detected in the cytoplasm of the supernatant of experimental cell culture. Cripto-1 was detected in the cytoplasm of L02 cell culture supernatant. Supernatant on exposure to Cripto-18 h or 12 h could increase IL-1 beta and TNF-alpha mRNA expression level (P<0.05), but the TGF-beta mRNA expression level was not higher (P>0.05). The mRNA expression levels of IL-6 and IL-10 were increased by Cripto-1, which was secreted into the supernutriment of cell lines (P<0.05). Exposed to such supernatant significantly increased the supernatant fluid IL 10 and TNF-alpha, IL-6 and IL-1β mRNA and protein expression level (P<0.05), but did not influence the TGF-β expression (P>0.05). Cripto-1 treated cells with higher nuclear p65 levels, ibb kinase (IKB) phosphorylation, and ibb phosphorylation (P<005). Conclusion Cripto-1 enhance phagocytic activity of macrophages induced by allogeneic transfusion through NF-kB signaling pathway, and up-regulate the production of anti-inflammatory and pro-inflammatory cytokines