Purpose: The current clinical study was done to examine clinical and biochemical changes of Vascular Endothelial Growth factor (VEGF) biomarker present in (GCF) in response to LLLT combined with Platelet Rich Fibrin (PRF) & bovine xenograft to treat infra-bony defects. Material and methods: The current study was conducted on twenty (20) sites from ten (10) patients. A spilt-mouth design used, sites were randomly selected from each patient, into two groups: laser group; ten (10) sites received PRF system without irradiation, and control group; ten (10) sites received PRF system and it will be irradiated with low level laser. Clinical parameters including probing pocket depth (PPD), clinical attachment level (CAL), Plaque index (PI), and gingival index (GI). ELISA quantification analysis of VEGF was done. Results: comparison between the groups at 6 months showed significant difference between both Probing depth and clinical attachment level, while Plaque index and Gingival index showed a significance difference starting from 2 weeks postoperatively. VEGF revealed no significant difference among groups. Conclusion: The using of low intensity laser with PRF system showed an improvement in the outcome of infra bony defects treatment.