Abstract Background Multi‐isocentric intensity‐modulated (IM) total body irradiation (TBI), total marrow irradiation (TMI), and total marrow and lymphoid irradiation (TMLI) are gaining popularity. A question arises on the impact of the interplay between blood circulation and dynamic delivery on blood dose. Purpose This study answers the question by introducing a new whole‐body blood circulation modeling technique. Methods A whole‐body CT with intravenous contrast was used to develop the blood circulation model. Fifteen organs and tissues, heart chambers, and great vessels were segmented using a deep‐learning‐based auto‐contouring software. The main blood vessels were segmented using an in‐house algorithm. Blood density, velocity, time‐to‐heart, and perfusion distributions were derived for systole, diastole, and portal circulations and used to simulate trajectories of blood particles during delivery. With the same prescription of 12 Gy in 8 fractions, doses to circulating blood were calculated for three plans: (1) an IM‐TBI plan prescribing uniform dose to the whole body while reducing lung and kidney doses; (2) a TMI plan treating all bones; and (3) a TMLI plan treating all bones, major lymph nodes, and spleen; TMI and TMLI plans were optimized to reduce doses to non‐target tissue. Results Circulating blood received 1.57 ± 0.43 Gy, 1.04 ± 0.32 Gy, and 1.09 ± 0.32 Gy in one fraction and 12.60 ± 1.21 Gy, 8.34 ± 0.88 Gy, and 8.71 ± 0.92 Gy in 8 fractions in IM‐TBI, TMI, and TMLI, respectively. The interplay effect of blood motion with IM delivery did not change the mean dose, but changed the dose heterogeneity of the circulating blood. Fractionation reduced the blood dose heterogeneity. Conclusions A novel whole‐body blood circulating model was developed based on patient‐specific anatomy and realistic blood dynamics, concentration, and perfusion. Using the blood circulation model, we developed a dosimetry tool for circulating blood in IM‐TBI, TMI, and TMLI.