For the artificial water flooding development reservoir that maybe has strong natural edge water and bottom water, it is very important to determine the optimal well ratio of injection to production considering the influence of the natural water influx in the design of reservoir development plan. No good reservoir engineering method is found to determine it. A new practicable method is presented: the optimal well ratio of injection to production is the well ratio that can make the reservoir being able to obtain the maximum ability of liquid production rate. According to the material balance principle, the liquid production is equal to the sum of the water injection and the water influx, so the objective function of the maximum amount of liquid production rate is established after a series of deriving and deduction of complex formulas, and then the optimal well ratio of injection to production is deduced under the conditions of meeting the objective function maximum. It is found that the optimal well ratio of injection to production is the function that is related to the bottomhole flowing pressure of injection well and production well, water injectivity index, fluid productivity index, the number of the whole reservoir wells, the natural aquifer body pressure and the natural water influx coefficient. It is also found that the well ratio of injection to production when the natural water influx coefficient is zero is just the well ratio of injection to production in injected and produced fluid balance. In the end, the optimal well ratio of injection to production is successfully calculated under different bottomhole flowing pressure conforming to the bottomhole flowing pressure limitations of injection well and production well for an example reservoir in Xinjiang oilfield. The results available can be used in guidance and reference to the next development adjustment, and this method can be applied to any reservoir with natural water influx and artificial water injection.