This paper proposes an optimal tuning of Power System Stabilizer (PSS) using Artificial Immune System (AIS) algorithm for damping oscillation of multi-machine power system. PSS is the efficient devices todamp the power system oscillations which are caused by interruptions. This study presents a robust algorithm to determine the PSS parameters using AIS algorithm. The PSS parameters tuning is usually formulated as the objective function with constraints, including the damping ratio and damping factor. Optimization with maximum value of the damping factor and the damping ratio of power system modes are taken as the goals functions, when designing the PSS parameters. This optimization procedure could enhance the cloning process and lead to a better outcome. In this work, the two-area multi-machine power system of IEEE model, under a wide range of system configurations and operation conditions is investigated. The system has been used to illustrate the performance of the proposed algorithm. The performance of the AIS-based PSS is compared to the Delta w PSS and Delta Pa PSS. The results verify that, AIS-based PSS, Delta w PSS and Delta Pa PSS gives relatively good in reducing oscillation system variables of which transfer electrical power, changes in angular velocity generator, and the generator terminal voltage. All PSS can work well in order to stabilize the system under interruption. However, AIS-based PSS have relatively better than Delta w PSS and Delta Pa PSS in terms of ability to reduce oscillation and speed of reaching a state of instability.