Aim: To assess the effect of Thymoquinone as anew chemopreventive and treatment modality on acrylamide (ARC)-induced striated muscle degeneration of rat's tongue, the present study was performed. Material and methods: Forty adult male albino Sprague-Dawley rats were used as experimental animals and divided into four equal groups (G(s)): 10 animals in each one for two successive periods (5 animals for 20 days: GA) and (the other 5 animals for 40 days: GB). The groups used were as follow: G1(A&B) {negative control group}, G2(A&B) {positive control group: ARC treatment group}, G3(A&B){Thymoquinone chemoprevention group}: ARC + Thymoquinone, alternatively} and G4(A&B) {Thymoquinone therapeutic group} In this group, animals were received ACR as mentioned in G2, followed by Thymoquinone (20 mg/kg) injection intraperitoneally once daily for 3 times as follow: first day, third day and the fifth day. After termination of the experiment, the tongue of the animals were examined then the animals were euthanized and the tongue were excised, fixed in 10% neutral buffered formalin, routinely processed and stained with hematoxylin and eosin (H&E) stain as well as with PTAH stain in order to be examined microscopically and histomorphometrically. Results: Gross observation revealed that there was a variation in the areas of swelling, redness and bleeding that ranged from small patches in G3, moderate in G4 to large areas in G2. Histopathological findings demonstrated various alterations in the pattern of muscle fibers in the groups used throughout the experimental periods. These alterations included abnormal wavy course of the muscle fibers with splitting of the myofibers and fragmentation of the sarcoplasm. The histomorphometric results revealed that PTAH staining has variability in the area percentage throughout the groups used. There were significant differences between G1 and G2A, G1 and G3A, G1 and G4A, G2A and G4A, G3A and G4A. In conclusions: Realization of striated muscle damage in rat`s tongue by ACR which becomes worse with prolonged duration. Moreover Thymoquinone has a significant protective effect when compared with its therapeutic effect on ACR-induced striated muscle injury of rat`s tongue.