In response to the demand for dry eye treatment by lacrimal duct embolization, this paper prepared the oxidized Pululan polysaccharide (OPL) by the Dess-Martin oxidation method, while ensuring the integrity of the sugar ring structure. A thermosensitive hydrogel OPL-HPCS-GP with interpenetrating structure by Schiff-base bond and hydrogen bond was prepared based on hydroxypropyl chitosan (HPCS) and sodium glycerophosphate (GP). Structure and morphology of hydrogels were characterized using 1HNMR, FTIR, SEM. Other properties such as mechanical properties, rheology properties, swelling properties, degradation properties, drug load and release, hemocompatibility, and cytotoxicity were also analyzed. The effect on lacrimal embolism of OPL-HPCS-GP hydrogel was evaluated by rabbit dry eye models. The results showed that OPL-HPCS-GP sol can rapidly transfer to gel with dense and uniform network structure at physiological temperature (37 ℃). The maximum stress (1.96±0.12) N and compression modulus (30.22±2.27) kPa of OPL-HPCS-GP hydrogel showed good mechanical properties. In simulated tear fluid, the equilibrium swelling rate of OPL-HPCS-GP was (209.50%±5.75%), the degradation rate was (25.18%±1.47%) within 60 d. The hemolysis rate of OPL-HPCS-GP hydrogel on sheep erythrocytes was (1.95%±0.11%), and the cell viability of L929 cells was (112.97%±2.64%), which indicating excellent biocompatibility. Compared with the New Zealand white rabbit autogenous dry eye group, the treated one injected with OPL-HPCS-GP was still able to maintain the TMH with 325 μm at 30 d which can improved the symptoms of dry eye.