Objective. To explore the effect and mechanism of the sponge dressing on the healing of refractory orthopedic wound, and the gelatin-Bletilla striata gum/Salvia miltiorrhiza nano Ag (GBS-Ag) sponge dressing was prepared. Methods. GBS-Ag sponge dressing was prepared by the freeze-drying method. Twenty male SD rats were randomly divided into the control group (Ctrl group) and GBS-Ag group, with 10 rats in each group, and the rats in the two groups were established a model of back wound infection. The Ctrl group was treated with gauze, while the GBS-Ag group was treated with GBS-Ag sponge dressing. Wound healing rate, blood immune indexes, Ag content in each organ, morphological changes of wound, and expression of transforming growth factor-β1 (TGF-β1) in wound transformation were detected in the two groups of rats. Results. The mechanical properties of GBS-Ag sponge dressing were all in line with the standard, and it had good killing effect on the conventional strain after being incubated for 24 hours. Compared with the Ctrl group, the healing rate and lymphocyte percentage in the GBS-Ag group were significantly increased on day 4 and day 10 (
P
<
0.05
), while the total number of white blood cells and the percentage of neutrophils were significantly decreased (
P
<
0.05
). Compared with Ctrl group, the Ag content in liver, spleen, and kidney of rats in the GBS-Ag group was significantly increased (
P
<
0.05
). The histological results showed that the Ctrl group lacked collagen fibers in the dermis, and the angiogenesis was not rich, accompanied by a large number of inflammatory cell infiltration. The epidermal repair of rats in the GBS-Ag group was complete and partially keratinized, the dermis was rich in collagen fibers, with elastic fibers and new blood vessels, inflammatory cells were rare, and new hair follicles and thick-walled blood vessels were also observed. The expression of TGF-β1 protein in the wounds of rats in the GBS-Ag group was higher than that of the Ctrl group. Conclusion. GBS-Ag sponge dressing had multiple effects of sterilization and promoting wound healing, and its mechanism may be related to promoting the TGF-β1 protein expression.