Silk sericin (SS) has been shown to promote collagen synthesis during wound healing, but it lacks antimicrobial activity. We investigated the effectiveness and the induction of the inflammatory mediators IL-1bβ and TNF-aα by SS, silver sulfadiazine (SSD) cream, and SS in combination with SSD cream on wound healing in rats. The results show that SS at 8% w/w partially inhibits SSD antibacterial activity. Treating wounds with a combination of SS and SSD did not induce significant wound size reduction when compared to other treatments. However, SS can promote collagen production in wounds even in the presence of SSD. Wounds treated with the combination of SS and SSD cream showed higher levels of IL-1β and TNF-α when compared to wounds treated by SS alone, but the differences were not significant. Although SS may decrease the antimicrobial effect of SSD, SS in combination with SSD cream has the benefit of promoting collagen production without generating significant levels of inflammatory cytokines.