The present study investigated the effects on reproductive and interrenal system by pentachlorophenol (PCP) using in silico and in vivo assays. Molecular docking results indicated interacting potency of PCP with steroid receptors (ER alpha, ER beta, AR, GR) but not Cytochrome P450 enzymes (CYPs). In the in vivo assay, sexually matured rare minnow (Gobiocypris rams) was exposed to environmental relevant concentrations of PCP (0, 0.5, 5, 50 mu g L-1). In male fish, 14-d exposure caused up-regulation of mRNA levels of hepatic er alpha, er beta, ar, gr, vtg and gonadal er alpha, vtg, ar, dmrt1, providing evidence for agonistic activities for steroid receptors by PCP. The up-regulated mRNA of gnrh, crf, pomc in the brain also indicated feed forward responses of the hypothalamic-pituitary-gonadal/interrenal (HPG/I) axis. However, at 28th d the feed-forward response of the HPG axis seemed eased back and the HPI axis showed negative feedback responses. Corresponding changes including increases of plasma steroid hormones, inhibition of spermatogenesis, and decreased RSI were observed in male fish upon 28-d exposure to PCP. In the females, a transition from feed-forward responses to negative feedbacks of the HPG/I axis was also indicated by the transcriptional profiles at 14th and 28th day. Corresponding changes including increased E2, T and decreased C levels, degenerated ovaries, and decreased GSI and RSI were also observed. Overall, we concluded that PCP could interfere with steroid receptors, evoke responses of HPG/I axis, and finally result in adverse effects on reproductive and interrenal system in rare minnow at environmental relevant concentrations. (C) 2016 Elsevier Ltd. All rights reserved.