Background: The antimicrobial photodynamic therapy (aPDT) inactivates the target cell via reactions among the photosensitizer (PS), Laser or Led and O 2 . The aim of this study was to evaluate the tissue reaction and cytokine production promoted by aPDT with curcumin photosensitizer. Methods: Polyethylene tubes containing saline solution (control), 5% sodium hypochlorite (NaOCl) and aPDT with curcumin PS 500 mg/L, were implanted into dorsal connective tissue of Wistar rats. After 7, 15, 30, 60 and 90 days of implantation, the animals were euthanized and the tubes with surrounding tissues were removed. The specimens were divided in two part, one half was processed, fixed and prepared for histological analysis by staining with hematoxylin and eosin. The other half was collected for IL-1β and IL-6 cytokine production using ELISA assay. The results were statistically analyzed by Kruskal-Wallis test followed by Dunn test (p < 0.05) for tissue reaction and ANOVA followed by Bonferroni's correction (p < 0.05) for ELISA. Results: All groups showed severe tissue reactions at 7 days, whilst a significantly decrease by time was observed. Regarding to cytokine production, aPDT increases the IL-1β levels in all periods of time (p < 0.05). However, for IL-6 levels, the highest value was observed with aPDT on the 90th day (p < 0.05). Conclusions: aPDT with curcumin PS 500 mg/L demonstrated biocompatibility similar to saline solution and induced the IL-1β and IL-6 cytokines production.