Abstract: In the process of voltage and reactive power control in substations, the reactive power control model established through a single regulation method is limited by the internal and external factors of the substation, and the reactive power balance is broken. The control values of reactive power and voltage on the high and low voltage sides deviate from the control expectations, which affects the operation quality of the substation voltage. Therefore, a voltage and reactive power automatic control method for substations based on multi-agent immune algorithm was designed. Intelligent reference to inherent and adaptive immune response conditions, establishing a voltage and reactive power control immune scheduling intelligent agent model for substations through dual layer regulation. Mapping the external and internal influencing factors encountered by multi-agent systems as "antigens", establishing on-site voltage and reactive power balance constraints for substations, and setting automatic voltage and reactive power control boundaries under multi-agent immune algorithms to achieve automatic voltage and reactive power control in substations. The final control results show that the reactive voltage on the high voltage side varies within the range of 1.0p.u.~1.15p.u., and the reactive voltage on the low voltage side varies within the range of 0.95p.u.~1.06p.u.. The control values are consistent with the expected values, and the automatic reactive power control effect is good.