The study investigated the effects of Qingguang’an II (a Chinese medicinal preparation) on expressions of OX42 protein and interleukin-1β (IL-1β) mRNA of retinal microglia cells of rats with chronic high intraocular pressure (IOP). SD rats were randomly divided into 6 groups, that were: A: blank group; B: model group; C: Qingguang’an II low dose group; D: Qingguang’an II medium dose group; E: Qingguang’an II high dose group; F: Yimaikang disket (a Chinese medicinal preparation) group. Experimental rats in B, C, D, E, F groups were established the model of chronic high IOP by cauterizing of superficial scleral vein. Tissues of eyes were obtained after intragastric administration for 2 and 4wk. At the time-point of 2wk, OX42 protein and IL-1β mRNA in group B were statistically expressed in higher level comparing with other groups (P<0.05). Moreover, at the time-point of 4wk, OX42 protein and IL-1β mRNA in groups C, D and E were statistically expressed in lower level comparing with group F (P<0.05). Besides, OX42 protein and IL-1β mRNA in groups C and D were statistically expressed in higher level comparing with group E (P<0.05). OX42 protein and IL-1β mRNA in groups C and D were expressed in similar level (P>0.05). The study indicated that, in the protection of optic nerve of rats with chronic high IOP, the high dose of Qingguang’an II at the time-point of 4wk was the better choice.