PURPOSE: To investigate the dynamics of Heat Shock Protein 72 (HSP72) expression in retinal ganglion cell (RGCs) and lateral geniculate nucleus (LGN) neuron in a model of chronic ocular hypertention treated with intraperitoneal injection of zinc sulfate and quercetin and to explore the mechanism of HSP72 neuroprotection in glaucoma. METHODS: 140 male Wistar rats were used to make chronic glaucoma models. 12 others served as normal control. Chronic glaucoma models were made by cauterizing the limbal episcleral veins to block the reflux of aqueous humor by 532nm viridis-lite laser. 48 model rats were killed at different intervals after laser treatment without drug injection, which served as damage control.30 were treated with zinc sulfate injection 2 weeks posterior to laser treatment; 30 were used for quercetin administration 6 hours posterior to laser treatment and 20 were treated with sp600125 posterior to laser treatment. Treated model rats were sacrificed at designed intervals after treatment. Right eyes were enucleated immediately. The retinas and LGN were dissected for HE, immunohistochemical, FluoroGold staining and Western blot.RESULTS: No HSP72 and no SAPK/JNK activation were found in RGCs and LGN neurons of normal Wistar rats. After laser treatment, HSP72 was detected significantly expressed in RGCs and LGN neurons posterior to laser treatment in damage control group. HSP72 production in RGCs and LGN neurons of zinc sulfate group were higher than the damage control,and yet quercetin group were significantly lower at every time point. The count of RGCs both zinc sulfate group and sp600125 group were higher than the damage control at every point(p<0.05), but the number of RGCs in zinc sulfate group was lower than the sp600125 group in treated eyes (p<0.05).p-JNK and p-c-jun expressions of damage control were visible at 3 day, and reached the peak at 7 day. Zinc sulfate administration decreased p-c-jun expression significantly, which was the same as sp600125, a JNK inhibitor. Quercetin injection enhanced the p-c-jun protein level. There was no significant difference of p-JNK activation in four experimental groups at every point, including damage control, zinc sulfate, quercetin and sp600125 treatments (P>0.05). In the LGN, p-JNK and p-c-jun expressions were visible at every time. p-JNK and p-c-jun dynamic expressions reac hed the peak at 14 day, which were the same as their expressions at 7 day in retina on activation.CONCLUSIONS: HSP72 protects chronic ocular-hypertensive rat model of RGCs and LGN neurons from injury by blocking SAPK/JNK pathway activation.