Objective To explore the healing effect of xiaochaihu decoction in a rat model of chronic pyogenic osteomyelitis of the jaw. Methods Sixty-five specific-pathogen-free rats were used to establish a model of chronic pyogenic osteomyelitis of the jaw, by introducing Staphylococcus aureus into round bone defects prepared using a bone drill. After 1 month, five rats were randomly selected to test the modeling result, and the other rats were divided randomly into four groups: group A, debridement+saline; group B, debridement+xiaochaihu decoction; group C, debridement+cefuroxime; and group D, debridement+xiaochaihu decoction+cefuroxime. Five rats in each group were sacrificed at 2, 4, and 8 weeks after administration. The extent of the bone defect was detected by cone beam computed tomography (CBCT), levels of the inflammatory cytokines interleukin (IL)-6 and IL-1β were detected by enzyme-linked immunosorbent assay, and bone morphogenetic protein-2 was detected by immunohistochemistry. Results CBCT showed that the bone defects in groups B, C, and D had decreased at 2, 4, and 8 weeks after administration, compared with group A (P<0. 05). In addition, the bone defects were smaller in groups B and D compared with group C (P<0. 05), and smaller in group D compared with group B (P<0. 05). Levels of IL-6 and IL-1β were lower in groups B, C, and D compared with group A at 2, 4, and 8 weeks after administration, IL-1β levels were lower in groups B and D compared with group C, and levels of IL-6 were lower in group D compared with C (P<0. 05); however, there was no significant difference in IL-6 levels between groups B and C ( P>0. 05). IL-1β and IL-6 levels were both lower in group D compared with group B (P<0. 05). BMP-2 expression was detected in groups A, B, C, and D, with higher mean optical densities in groups B, C, and D compared with group A, higher optical densities in groups B and D compared with group C, and in group D compared with group B at 2, 4, and 8 weeks after administration (P< 0. 05). Conclusions We successfully established a rat model of chronic pyogenic osteomyelitis of the mandible using S. aureus. Xiaochaihu decoction improved chronic pyogenic osteomyelitis, and the therapeutic effect of xiaochaihu decoction combined with cefuroxime was better than that of either drug alone.