Abstract: Using Injection?production system of horizontal wells in low permeability reservoirs by water drive process can solve many problems from vertical wells, such as small well spacing and limited well?controlling reserves, etc., hence obtaining good economic benefits. At present, the mature method for calculation of reasonable injection?production well spacing is not yet found for such a kind of reservoirs by adopting horizontal well to run water flood development. Based on oil?water two?phase flow, non?piston drive and oil production, this paper proposes a new method for determination of such a reasonable well spacing by using the two?phase flow mathematical expression, regarding the sum of water flooding front and injector distance and well drainage pressure swept distance as basis of the reasonable well spacing by mathematical derivation. The case study shows that the relationship between the reasonable well spacing and the permeability is well simulated by power function, and the horizontal well spacing is much longer than the vertical well spacing