Objective To investigate the effects of SHP-2 D61G / + mutations on leukocyte infiltration，cytokines secretion and multi-organ impairment． Methods The SHP-2 D61G / + gain-of-function mutant gene knock-in model mice and wild-type 57BL /6 mice ( WT) were used in this study． Serum level of IL-2 and TNF-α and the cytokines concentration in the supernatant of cultured WBC were quantified by enzyme-linked immunosorbent assay ( ELISA) ． Leukocyte infiltration in the lung，spleen and heart tissues was observed by histopathology，and serum levels of alanine aminotransferase ( ALT) and cardiac troponin I ( cTnI) were studied by radioimmunoassay． Results Compared with the WT control，leukocyte infiltration in the lung and spleen tissues were significantly increased and myocardial hypertrophy was observed in the SHP- 2 D61G / + mutant mice． The serum levels of IL-2 and TNF-α were significantly increased in SHP-2 D61G / + mutant mice ( P ＜0. 01，compared with the WT control) ，and so were the cytokines concentrations in the supernatant of cultured WBC ( P ＜0. 01，compared with the WT control) ． The serum levels of ALT and cTnI were significantly higher in the SHP-2 D61G / + mutant mice than that of the WT controls ( P ＜ 0. 01 ) ． Conclusions Gain-of-function mutations in SHP-2 tyrosine phosphatase ( SHP-2 D61G / + ) greatly induce leukocyte infiltration in tissues，IL-2 and TNF-α secretion and multi-organ impairment，which may lead to multiple organ failure．