Background: In this work, a low-dose rate (100mGy/min of whole body gamma irradiation fractionated (0.5, 1, and 2Gy) was used to study the effects of cumulative doses on the expression of target genes implicated in the intestinal inflammatory process in high fat diet (HFD) wistar rats. Material and Methods: Total RNA was extracted and the expression of target genes was measured in the four intestinal segments (duodenum, jejunum, ileum and colon) of HFD Wistar rats. Results: Our in-vivo results in the four intestinal segments (duodenum, jejunum, ileum, and colon) demonstrated that gamma irradiation exposure in HFD rats amplified the low-grade inflammatory state already induced by HFD. This phenomenon occurs through the induction of pro-inflammatory cytokines mainly the tumor necrosis factor-alpha (TNFα) and interleukin 6 (IL-6) or via overexpression/increasing of anti-inflammatory response involved interleukin 10 (IL-10) and the growth factor β (TGFβ) overall the bowel segments. Results suggested that whole body gamma irradiation might have dual roles, first, engraving the inflammatory state already initiated by HFD, and second, an over expressed anti-inflammatory response via anti-inflammatory cytokines mainly IL-10 and TGFβ. Conclusion: The current study clearly demonstrated the important role of the gut in HFD rats during fractionated whole body irradiation (FWBGI) and indicated that TGFβ and IL-10 may be the target in whole body radiotherapy as a mechanism to recompense for the ‎imbalance between pro-inflammatory and anti-inflammatory cytokines.