Abstract: Objective To understand the histopathologic changes and cytokine secretion in the foot pads of mice infected with Nocardia farcinica at different times and the pathogenic mechanism of Nocardia farcinica. Methods The foot pads of mice were infected with Nocardia farcinica in logarithmic phase to establish an infection model. A mouse was killed and the foot pad was cut off with surgical blade at day 1, 3, 7 and 14 after infection. The foot pad tissues were collected and embedded in paraffin. Pathological changes were assessed by HE staining and the cytokines of IL-6, IL-12, IFN- and TNF were detected with immunohistochemistry assay. Results The results of HE staining showed that at day 1 after infection, neutrophil infiltrated and inflammation occurred; at day 3 after infection, neutrophils abscess was presented and it was the period of acute infection; at day 7 after infection, there were amount of myofibroblast and endothelial cells hyperplasia in the focus of infection and it was the period of chronic infection; and at day 14 after infection, besides the myofibroblast and endothelial cells hyperplasia, focal abscesses was formed and macrophage-derived foam cells was found. It was the period of recovery. The results of immunohistochemical detection indicated that in the inflammation phase, the expression levels of IL-6 and TNF were higher than those of control group (P0.05), in acute phase, only TNF expression level was higher than control group (P0.05), in chronic phase, the expression levels of IL-6,IL-12, IFN- and TNF were all higher than those in control group (P0.05) and in recovery phase, the expression levels of IL-6, IFN- and TNF were higher than those in control group (P0.05). Conclusion The pathological change of mice foot pad infected with Ncardia farcinica was obvious. At 3, 7 and 14 day after infection it was acute phase, chronic phase and recovery phase respectively. IL-6, IFN- and TNF involved in inflammation, especially the IL-6.