Abstract Background: Rats are frequently used to study the pharmacological and toxicological effects of inhaled aerosol particles. The deposition behavior of aerosol particles in airways is affected by their hygroscopic properties, which accordingly influence the results of such studies. Method: A recently published nonhygroscopic aerosol particle deposition model for rat airways was extended with equations for hygroscopic particle growth in humid air and with a model to mimic the temperature and relative humidity conditions in the rat airways transformed from the upper human airways. As there are no experimental data available for hygroscopic deposition in rat lungs, several model assumptions were made for the humidity distribution in the upper rat airways. Results: The total and regional deposition probability of salt particles in the diameter range 0.02 to 5 μm in rat lung was significantly changed by the hygroscopic properties. The maximum ratios of the total deposition of inhaled initially dry sodium chloride, cobalt chloride, and zinc sulfate particles compared with nonhygroscopic particles were 3.28, 2.44, and 2.13, respectively, and the minimum ratios 0.57, 0.63, and 0.70, respectively. The corresponding maximum (and minimum) ratios for the hygroscopic drugs histamine dihydrochloride, carbenicillin disodium, and atropine sulfate were 1.86 (0.65), 1.53 (0.70), and 1.35 (0.76), respectively. Total deposition was about 20% higher in human airways than in rat airways. The flow regime in the rat upper airways influenced total and regional deposition much less than it did in human airways. Conclusion: The hygroscopicity of salt and drug aerosol particles is an important factor in rat lung deposition.