AIM: To investigate the significance and function of IFN-γ on the changes of peripheral blood platelet count during tumor-rejection induced by a low dose of melphalan in C57BL/6 mice. METHODS: Mouse tumor rejection model induced by a single dose of melphalan was used in this experiment. Different gene-type tumor-bearing mice (IFN-γ~(+/-) and IFN-γ~(-/-)), which had the same genetic background of C57BL/6, were treated intraperitoneally with melphalan (7.5 mg/kg). Tumor size was observed and recorded every one to three days in these different gene-type mice subsequently. Blood samples were obtained from orbital venous sinus on different days before and after melphalan treatment, and then complete blood counts were performed. The function of IFN-γ on the efficacy of chemotherapy and the changes of blood platelet count in IFN-γ~(+/-) and IFN-γ~(-/-) mice after melphalan treatment was analyzed. RESULTS: There was no significant difference in tumor sizes and blood platelet count between IFN-γ~(-/-) and IFN-γ~(+/-) mice (P>0.05). On the first day after melphalan (7.5 mg/kg) treatment, there were no significant changes in tumor sizes between mice in these two groups (P>0.05). Tumors shrank a little in IFN-γ~(-/-) mice and then grew gradually. Tumors relapsed in 2 w after melphalan injection in all IFN-γ~(-/-) mice, while tumor volumes decreased progressively and tumor cured at last in IFN-γ~(+/-) mice. The number of blood PLT in IFN-γ~(+/-) mice increased to (1935±378)×10~9/L 6 h after melphalan treatment, significantly higher than before (P<0.01); While in IFN-γ~(-/-) mice it was (1183±186)×10~9/L 6 h after melphalan treatment, no obvious increase than before. There was significant difference in blood PLT 6 h after melphalan treatment between IFN-γ~(+/-) and IFN-γ~(-/-) mice (P<0.01). Later, the numbers of blood PLT in IFN-γ~(+/-) mice decreased gradually and it dropped to normal (1158±270)×10~9/L on 11th day after melphalan treatment (P>0.05); While it sustained in normal range in IFN-γ~(-/-) mice. There was no significant difference in blood platelet count between IFN-γ~(-/-) and IFN-γ~(+/-) mice. CONCLUSION: Peripheral blood platelet count increased on the first day after melphalan treatment and tumors cured in IFN-γ~(+/-) mice; While tumors relapsed and there is no increase in blood platelet count on the first day after melphalan treatment in IFN-γ~(-/-)mice. These data indicated that the increase of blood PLT count was related to the function of IFN-γ in tumor-bearing mice in vivo during tumor rejection induced by a low dose of melphalan.