Objective  To investigate the effect of voluntary wheel running on negative affective of mice induced by formaldehyde.    Methods  Thirty male Kunming mice were randomly divided into three groups, including normal saline control group (NS), formaldehyde model group (F), and voluntary wheel running with formaldehyde injection group (R+F). The pain model was established by right hindpaw intraplantar formalin injection, the mice of R+F group experienced voluntary wheel running for three weeks before intraplantar formaldehyde injection. The spontaneous pain behavior was determined by the cumulative time of licking paw. The anxiety-like behavior of each group was determined by open field test (OFT) and elevated plus-maze test (EPM) while the depression-like behavior of each group was determined by forced swimming test (FST). The expression of doublecortin（DCX）in the hippocampus was determined by immunohistochemistry.    Results  Compared with the NS group, the typical two-phase pain response was observed in the F group, and compared with the F group，the second phase pain duration was significantly reduced in the R+F group (P<0.01).  In the open field test, the F group showed remarkably reduced time in the inner area(P<0.001) compared with the NS group, while the R+F group increased time in the inner area (P<0.05) compared with the F group. In the elevated plus-maze test, the F group showed remarkably reduced time (P<0.001)spent in the open arm compared with the NS group，however，compared with the F group, R+F group increased time spent in the open arm (P<0.05). In the forced swimming test, the immobility time of the F group significant increased (P<0.01) compared with the NS group, which was decreased in the R+F group (P<0.05). The Immunohistochemistry showed that the area of DCX positive cells in the hippocampus of the F group was downregulated compared with the NS group, which was upregulated in the R+F group.    Conclusion  Our findings indicate that voluntary wheel running can improve anxiety and depression-like in mice induced by formaldehyde injection, which may be related to enhanced neurogenesis in the hippocampus.