In the current study, we aimed to evaluate the efficacy of the treatment of the dairy cows suffering from endometritis using nano-oxytetracycline (OTC-NPs), platelet-rich plasma (PRP), and conventional oxytetracycline (OTC) based protocols. To accomplish this study a group of 30 cycling Holstein lactating dairy cows suffering from post-partum endometritis were divided into three equal groups. Group I was given 10 ml of nano-oxytetracycline intrauterine infusion, two doses with one week interval, group II was treated with three doses of 20 ml of oxytetracycline 5% intrauterine infusion at one week interval and group III was given two doses of 10 ml of their own platelets rich plasma (PRP) one week apart and third one in day four post estrus. Results showed that serum level of TNF-α and IL6 recorded a significant decrease in all treated groups and the higher average decrease was recorded in group-I followed by group-III and finally group-II. In addition, all the treatment protocols significantly and successfully decreased the uterine thickness as compared to uterine thickness before treatment. In conclusion, and based on the changes in serum pro-inflammatory cytokines level, treatment with nano-oxytetracycline was more efficient in treatment of endometritis, followed by PRP and finally the conventional oxytetracycline.