Laser shock peening (LSP) is an advanced surface modification technique for anti-fatigue manufacturing. In this paper, the orthogonal test method was employed to investigate the distribution of residual stress on the surface of 2050 aluminum-lithium alloy. The correspondingly optimal LSP parameters were obtained. Furthermore, the fatigue life extension was verified with these parameters. Results show that there is a strong correlation between the LSP-induced residual stress and the geometric characteristics of the specimen. For the LSP parameters which affected residual stress, the effect of overlapping rate is greater than laser energy, and further more significant than impact times. The optimal LSP parameters are laser power density of 5.30 GW·cm^-2, overlapping rate of 50%, and peened twice. With the optimal LSP parameters, the fatigue life increased by 22% and 63% at 260 MPa and 200 MPa stress level, respectively.