Objective : To examine the impact and partial mechanism of bupivacaine sustained-release drug ( code PB21) in combination with low-dose dexamethasone ( Dex) on the analgesic time of rats with knee osteoarthritis (KOA) ． Methods : Using the techniques of anterior cruciate ligament transection and meniscus instability，a rat KOA model was created．After eight weeks，SD mice were split into three groups at random : a group for the model， one for Dex (50 μg) ，one for PB21 ( 1. 5 mg) ，and one for combined administration ( 1. 5 mg PB21 /50 μg Dex) ， with a control group that received a sham operation．The pain thresholds of KOA rats were measured using a Pres- sure Application Measurement (PAM) at different intervals before to delivery and 4，24，36，and 48 hours following administration ; to gauge changes in discomfort，a CatWalk was used to assess the rats' average foot strength and maximum contact area before，four，twenty-four，and forty-eight hours after treatment．A portion of the rats were put to sleep at four，twenty-four，and forty-eight hours following the injection，and the joint synovium was removed for paraffin sectioning．Immunohistochemistry was used to identify the expression of GAP43 in the synovium，whereas immunofluorescence was used to identify the expression of CGRP in the same tissue. Results : The average strength and maximum contact area of the foot and claw decreased (P ＜0. 01 ) ，and the pain threshold decreased (P < 0. 01) in the model group compared to the sham operation group．The PB21 + Dex group experienced a delayed pain threshold lowering time delay when compared to the PB21 and Dex treatment groups alone．Up to 48 hours lat- er，the combination administration group's average strength and maximum contact area of the foot paw remained ele- vated，and there was a statistically significant difference (P ＜0. 05 ) between the combined administration group and PB21 and Dex alone．GAP43 and CGRP expression levels in synovial tissue were detected．The results indica- ted that PB21 and Dex alone could lower protein expression levels at 4 and 24 h at the two time points，and that the PB21 + Dex group could still significantly lower GAP43 and CGRP expression levels at 48 h．At the 48 h time point，the PB21 + Dex group was statistically significant when compared to the PB21 and Dex alone administration group(P＜0. 05) ． Conclusion In summary low dose dexamethasone can prolong the analgesic effect of PB21 on KOA rats，which is connected to reducing the expression of pain related proteins CGRP and GAP43 .