Silk proteins have been shown to be good candidates for biomedical materials. However, there have been some reports regarding immunological and allergic responses to silk sericin. Our objective was to investigate the inflammatory mediators induced by sericin both in vitro and in vivo. Mouse monocyte and alveolar macrophage cell lines were used for monitoring levels of interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha generated after activation by sericin at concentrations of 0.2-1.0 mg/mL. The amounts of TNF-alpha and IL-1beta produced by both cell lines corresponded, in a dose-dependent manner, with the sericin concentration in the culture medium. The levels of TNF-alpha and IL-1beta generated after sericin activation by macrophage cells were higher than those generated by monocytes. However, these cytokine levels would not cascade to other inflammatory effects. Inflammatory mediators were also monitored from sericin-treated, cream base-treated and normal saline-soaked full-thickness rat excisions. Using wound size measurements and ELISA assays, sericin-treated wounds were shown to heal faster and had lower levels of inflammatory mediators, as compared with the cream base-treated and normal saline-soaked wounds. It can be concluded that sericin promotes the wound healing process without causing inflammation.