In this study, we investigated the physico-biological and in-vivo evaluation of irisin loaded 45S5 bioglass bone graft for enhancing osteoblastic differentiation and bone regeneration in rat femur head defect model. Highly porous structure was obtained in the bioglass by burn-out process with varying the concentration of poly (methyl methacrylate) (PMMA) spheres. 10 % polyvinyl alcohol (PVA) was used as a binder for the sustain releasing of irisin on porous bioglass. Different concentrations of irisin were loaded on the selected bioglass samples and these were further evaluated for the biocompatibility and osteoblastic differentiation properties. The in vitro results demonstrated not only its biocompatibility but also that it stimulated pre-osteoblast differentiation. The in vivo data showed new bone formation as well as expression of osteogenic proteins like alkaline phosphatase (ALP), Runt-related transcription factor 2 (Runx-2), osteopontin (OPN), and collagen-1 (Col-1). Our results support the use of irisin loaded bioglass for the use of early bone regeneration.