Xiangpi Shengji Onitment (XPSJO) is a hospital preparation commonly used in clinic to treat large areas of bedsores and chronic non-healing wounds. However, a complete understanding of the molecular mechanisms is still lacking. This study used rats to explore the healing mechanisms of XPSJO in promoting infected wound healing. Forty-five male Sprague Dawley (SD) rats were randomly divided into model control group, XPSJO group and basic fibroblast growth factor (bFGF) group. The wound contraction was quantified on days 3, 7 and 14 after medication. Hematoxylin and eosin stains were performed for histopathological evaluation. The levels of tumour necrosis factor-α (TNF-α), interleukin (IL)-1β, matrix metalloproteinase 2 (MMP2), MMP9 and vascular endothelial growth factor (VEGF) were detected by enzyme-linked immunosorbent assay (ELISA). Protein expression of PI3K, p-PI3K, AKT, p-AKT and HIF-1α were detected by western blot analysis. XPSJO significantly enhanced the wound healing rate, and more blood vessels and fibroblasts were observed in the regenerated tissues in XPSJO treatment group. ELISA results showed that XPSJO significantly decreased the levels of TNF-α and IL-1β and increased the levels of VEGF in wound tissue. XPSJO increased the levels of MMP2 and MMP9 in early stage of wound healing. In addition, activated PI3K/AKT/HIF-1α signaling pathway was detected in the XPSJO treatment group.