Objectives: Interferential therapy (IFT) is a common electrophysical agent used by physiotherapists for pain management. However, there is ongoing debate regarding the hypoalgesic and neurophysiologic mechanisms by which IFT reduces pain. This study aimed to investigate the effect of IFT on plasma beta-endorphin (BEND) levels in the rat model as a proposed analgesic mechanism of IFT. Methods: Twelve adult male Wistar rats received an intra-plantar injection of 0.15 ml of Freund's complete adjuvant (FCA) into the right hind paw under anaesthesia. Five days post FCA, the rats were anesthetized and were divided into two groups (n = 6). One group received IFT at 4 Hz for 20 minutes on the inflamed paw while the other group received sham IFT. One ml of blood was withdrawn from the tail vein of both groups before IFT application but after anaesthesia and then again at the end of the 20 minutes of IFT/sham IFT. Collected blood was centrifuged and plasma was removed for analysis of BEND. Concentrations of BEND were measured in the plasma using ELISA radioimmunoassay. Results: There was a slight increase in the BEND levels in the treatment group following 20 minutes of IFT. However, this increase was not statistically significant neither within (Z = -0.314, P = 0.753, Wilcoxon test) or between the treatment and sham groups (Z = -0.363, P = 0.79, Mann-Whitney U test). Conclusion: The findings suggested that the release of plasma BEND may not be the mechanism by which 4 Hz IFT have an analgesic effect.