Based on the operational performance of hollow fiber membrane, backflushing flow (BF) and backflushing pressure (BP), the two key parameters of cleaning in line (CIL) were experimentally investigated in this paper. It was assumed that the optimal parameters should meet the requirement for delivering cleaning agents to the most distant fiber surface. Based on Hagen-Poiseuille theory, the equation derivation of the CIL operation shows that when the membrane backflushing flow (pressure) is fixed, the corresponding BF and BP have an optimal value range which the design of the BF and BP could base on. The permeability recovery of cleaning with sodium hypochlorite, assessed at low and high flow (pressure), indicated that operation at a more conservative flow (pressure) could conserve energy. With the flow (pressure) increased experimentally, an interesting phenomenon was found that the effective backflushing length first presents a short increase followed by a downswing. Meanwhile, the effect was investigated to prove that as fiber length increased, the backflushing time also increased. Moreover, when taking into account both the flux recovery and hysteresis time, operation with constant flow outperformed that with constant pressure under the optimal parameters. Finally, a mathematic model was developed to verify the former conclusion by comparing the theoretical value with the experimental value. Crown Copyright (C) 2013 Published by Elsevier B.V. All rights reserved.