Injectable platelet-rich fibrin (i-PRF) is an effective biological material that positively contributes to angiogenesis, wound healing, inflammation, regeneration processes, etc. This research aimed to evaluate the effect of i-PRF in rats with experimental periodontitis. Following the development of ligature-induced periodontitis, 24 Wistar albino rats were divided into three groups. Group-1: scaling and root planing (only-SRP); Group-2: SRP + i-PRF; Group-3: only- i-PRF. Heart blood from six donors was used for the i-PRF application. i-PRF was administered as a subgingival injection in the relevant groups on the 1st, 3rd, and 7th days. The tissues were evaluated histopathologically and immunohistochemically. Also, bone structures were examined using micro-CT. According to the data obtained, no statistically significant difference was observed among the groups in terms of bone resorption, inflammation, bone volume, bone levels (mesial/distal), and IL-1 beta, IFN-r, TNF-alpha, VEGF values (p > 0.05). However, bone mineral density was statistically significantly different among the groups (Group3 > Group2 > Group1) (p < 0.0001). Subgingival injection of only-i-PRF showed promising results in periodontitis treatment but contribution to SRP has not been proved according to this study results. The study results suggested that the i-PRF application was as effective as SRP in reducing bone loss, modulating inflammatory process, and effecting cytokines in experimental periodontitis. The significant effect of i-PRF on bone mineral density was the most remarkable result.