Abstract: Some (5-arylalkylidene-4-oxo-2-thioxothiazolidin-3-yl)acetic acids were prepared as potential antimicrobial compounds. General synthetic approach of all synthesized compounds is presented. All the discussed rhodanine-3-acetic acid derivatives were analyzed using the reversed phase high performance liquid chromatography (RP-HPLC) method for the lipophilicity measurement. The procedure was performed under isocratic conditions with methanol as an organic modifier in the mobile phase using end-capped non-polar C18 stationary RP column. RP-HPLC retention parameter log k (the logarithm of capacity factor k) is compared with log P values calculated in silico. The relationships between the lipophilicity and chemical structure of the studied compounds are discussed as well.