Abstract Background Osteoporosis may occur by using glucocorticoids for a long time. Recently, platelet-rich plasma (PRP) is used in treating a wide variety of musculoskeletal problems. Aim This work aimed to study the effect of PRP against dexamethasone-induced osteoporosis in adult male albino rats. Materials and methods This study was carried out on 40 adult male albino rats that were divided into two main groups: control group I: included 10 rats and experimental group II included 30 rats, which were subdivided into three subgroups. Subgroup IIa received PRP, subgroup IIb was injected with dexamethasone intramuscularly, and subgroup IIc received the same dose of dexamethasone and then injected with PRP. At the end of the experiment, upper ends of femur bones of all animals were obtained and processed for histological study using light and scanning electron micrograph studies. Results Light microscopic examination revealed osteoporotic histological changes in group IIb where cancellous bone trabeculae appeared thin and discontinuous. Scanning electron micrograph studies confirmed the results of the light microscopic study. Group IIc revealed partial preservation of the normal histological picture. Statistical analysis showed that group IIb and untreated left femur of group IIc revealed a highly significant decrease in the mean thickness of trabeculae and a highly significant increase in the width of intertrabecular spaces as compared with the control group, while group IIa and treated right femur of group IIc revealed nonsignificant changes as compared with the control group. Conclusion Osteoporosis resulted from glucocorticoids in adult male albino rats could be partially treated with PRP injection.