Statement of the Problem:Melatonin loaded PLA-Nano particles are nowadays important in biological system for it’s biodegradable nature in the mammalian system for systemtic/targetted drug delivery system. The aim of the present study is note the effect of Mel-PLA-Nano particles and toxicity in osteoprosis which is a lesser explored area of research. Methodology & Theoretical Orientation:Different concentrations of commercially available melatonin and PLA were prepared by dissolving in dichloromethane (DCM). The final dried nano-paticles were stored at 4°C for future use and a part was used for structural analysis by Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), Fourier Transform Infrared Spectroscopy (FTIR). Further, to evaluate the toxicity and immunological impact of nano-particles on rats; animals were divided into 2 groups (control and nano-particle treated, n=5/group) for 7 days. After treatment animals were sacrificed and blood, liver and kidney were collected. A fraction of blood was processed for assessment of cell mediated immune parameters (TLC, DLC and % LC) and remaining blood was centrifuged at 3000 x g at 4°C for 30 min. Plasma was seperated and used for evaluation of cytokines, (IL-2, IL-6, TNF-α, IFN-γ, IL-1β), makers of renal function test (urea, creatinine and BUN). Both plasma and tissue homogenates were used for estimations of AST, ALT, ACP and ALP. The nano-particle size was evaluated by SEM and TEM and was further confirmed by FTIR and in vitro controlled drug release efficasy.Findings:We noted signifacntly high (p < 0.05) levels of cell mediated immune parameters (TLC, DLC and %LC) and cytokine parameters (IL-2 and TNF-α) upon nano-particle treatment. But rest of the parametrs were found to be significantly low (like IL-6, IL-1β, AST, ALT; p > 0.05) or un-affected (like IFN-γ, ACP and ALP). Conclusion & Significance:From our preliminary study we may conclude that we have successfully synthesized Mel-PLA-nano-particles and their physilogical effects were non-toxic to the animal.