Purpose: To investigate early time effect of local radiation on the entire normal bone marrow through microPET. Methods: Six 16 week‐old BALB/c female intact mice were used for this study. PET acquisition with 18F‐FDG was performed on day 2 after 16 Gy of local irradiation to both hind legs while other regions were completely shielded with lead. The delivered dose was verified with TLD and EBT3 film. Inveon small animal scanner (Siemens) was used for microPET scanning. The mean dose of 1 8F‐FDG was 18.8 ± 1.6 MBq. The scan was started at 30 minutes after the injection under anesthesia. About 10 μl of a whole blood sample from the tail vein was taken after the end of the scan. OSEM3D/FastMAP was used for the reconstruction. There are eight region of interest: skull, mandible, humerus, cervical, thoracic, lumber, femur and tibia. The SUV value was normalized by the blood activity to consider individual biological decay difference and compensate injection fluctuation for each mouse. The uptake change in 1 8 F‐FDG before and after radiation was analyzed by mixed effects ANOVA, conducted using SAS proc mixed (version 9.2). Results: Radiation decreases 1 8 F‐FDG uptake over the all regions (< 0.0001) on day 2 after irradiation. Though the degree of change is different individually, the uptake after irradiation is 46% of its pre‐radiation level. The degree of 1 8 F‐FDG uptake of pre‐and post‐radiation differs among the bony regions (< 0.0001). The irradiated region, especially the tibia, significantly changes 18F‐FDG uptake, which is 29% of its pre‐radiation level. The uptake pattern over the bony regions is changed before and after irradiation. Conclusion: Local radiation changes 18F‐FDG uptake of entire skeleton in this experimental rodent model suggesting that bone marrow functions are significantly affected by the local radiation at an early time point.