Prangos fedtschenkoi (Regel et Schmalh.) Korovin (Apiaceae) is an endemic species for mountainous Middle Asia, which is both a rare and useful plant. Organic extractions from this species are being used in pharmaceutics and cosmetology. In recent years, P. fedtschenkoi distribution area has considerably decreased, presumably, resulting from human activities such as agriculture, construction works, overgrazing and collection from wild for pharmaceutic purposes. Six populations were found in Uzbekistan and their genetic divergence and differentiation were studied with 10 inter-simple sequence repeat (ISSR) markers, selected out of 101. Totally 166 amplified ISSR fragments (loci) were revealed, of which 164 were polymorphic. Relatively moderate level of polymorphism was found at population level with polymorphic bands ranging from 27.71% to 47.59%. Mean P = 39.05%, $N_a=1.40$, $N_e=1.25$, S.I. = 0.21, and $H_e=0.14$ were revealed for all loci across six populations. AMOVA showed higher variation among populations (62%) than within them (38%). The Bayesian model determined 5 clusters, or genetic groups. The posteriori distribution of the Theta II estimator detected full model identifying high inbreeding, intensified by low gene flow (Nm = 0.3954). Mantel test confined population 6 as distinct cluster corresponding to geographic remoteness (R = 0.5137, $p{\leq}0.005$). Results were used as the bases for developing conserve measures to restore populations.