Background: Pretreatment with lithium in thyroid cancer patients before radioiodine therapy (RIT) has been suggested to improve the results of therapy in terms of higher radiation to thyroid tissue and limiting extra-thyroid irradiation. Materials and Methods: The beta and gamma radiation to the thyroid gland and lungs in 8 female New Zealand rabbits weighing 2.7 to 3.6 kg were simulated employing GATE Monte Carlo code. The study design was before-after and crossover; rabbits were orally treated with 165 to 288 µCi ¹³¹I with or without pretreatment with 60 mg per day lithium. SPECT/CT imaging was done 20 to 24 hours after RIT providing the distribution and attenuation maps for simulation. The S-values were calculated and compared between the rabbits prepared with and without lithium before RIT by analysis of covariance. Results: For beta radiation, the thyroid to lung S-value ratios (TLR) was 10.5 ± 1.6 with lithium pretreatment and 15.9 ± 12.5 without it. For gamma rays, TLR was 4.8 ± 1.8 vs. 6.7 ± 3.1 in rabbits with and without lithium pretreatment. The values of TLR were higher without lithium pretreatment but statistically insignificant. Conclusion: Lithium demonstrated no improvement in radioiodine uptake in thyroid tissue. Pretreatment of differentiated thyroid cancer patients with lithium before RIT, which is backed by old literature, should be reconsidered.