This study aims to explore the analgesic and anti-inflammatory effects of borneol, a traditional Chinese medicine, on photodynamic treatment of acne. Here, we found that borneol significantly decreased the auricular swelling rate and pain threshold of rats. We also showed that borneol noticeably reduced macrophage and lymphocyte infiltration. The number of Th cells was significantly higher in the control PDT group than in the PDT plus borneol treatment group (P < 0.05). The expression of IL-6, TNF-α, and IL-8 mRNA and proteins were noticeably lower in the treatment group in comparison to those of the PDT control group, while PDT plus borneol activated the p38-COX-2-PGE2 signaling pathway, increasing expression in the treatment group. Borneol has significant analgesic and anti-inflammatory effects on PDT of acne, and enhances the healing of acne by activating p38-COX-2-PGE2 signaling pathway.