Objective To study the effect and mechanism of Dl-3-n-butylphthalide(NBP) on mem-ory and learning ability in type 2 diabetes model db/db mice. Methods Sixteen male db/db mice were ran-domly divided into the NBP group and diabetes group,with 8 mice in each group. Eight male db/m mice of the same age were treated as the control group. NBP group was given NBP by gavage,while diabetes group and control group were given equal volume vegetable oil by gavage. After 6 weeks treatment,Morris water maze was used to examine the spatial memory and learning ability of the mice in each group. The changes of long-term potentiation ( LTP) in the hippocampus area of mice were detected by electrophysiological tech-niques. RT-PCR and Western blot were employed to measure expressions of VEGF,caspase-3,and Aβ1-42 in hippocampus of mice. Results Compared with the control group((21. 49±4. 41)s),average escape la-tency of day 5 in the diabetes group and NBP group were increased significantly ((51. 69±5. 45)s,(26. 92± 4. 76)s,t=9. 21,2. 35,both P<0. 05). Compared with the control group(7. 00±0. 60),the number of cross-ing the target platform in the diabetes group and NBP group were decreased significantly(2. 34± 0. 27), (4. 95±0. 54),t=-6. 56,-2. 49;both P<0. 05). Compared with the control group((255. 90±54. 24)%), LTP level in hippocampus of the diabetes group and NBP group were significantly decreased ( 130. 97 ± 14. 08)%,(176. 17 ± 18. 96)%,t=-4. 25,-2. 38; both P<0. 05). The relative expression of VEGF, caspase-3,and Aβ1-42 in the diabetes group and NBP group were significantly increased compared with those of the control group (t=4. 59,8. 42;7. 36,3. 85;3. 84,2. 11;all P<0. 05). Compared with the diabetes group,the escape latency of day 5,the number of crossing the target platform and LTP level were improved in the NBP group (t=-7. 25,4. 06,3. 25;all P<0. 05). The decreased expression of caspase-3,Aβ1-42 and increased expression of VEGF were reversed after NBP treatment in db/db mice (t=-4. 14,-2. 31,3. 42;all P<0. 05). Conclusion NBP might improve cognitive function and LTP by exerting anti-apoptosis effect through inhibiting the deposition of Aβ1-42 and upregulating VEGF expression in hippocampus of db/db mice.