Fatigue crack propagation in marine structures is obviously governed by mechanics of the considerably different four levels of multi-scale problems. Problems of structural response to environmental loads have length scale of several hundred meters, whereas possible detectable size of cracks from initial defects in a weld is of the order of millimeters. Once a fatigue crack initiates, crack tip plasticity is of the order of several grain sizes, while the resulting fatigue crack growth in each load cycle is of the order of nanometers. In our previous work, the first author and their associates have developed the so-called CP-System, which can treat the first two multi-level problems as an integrated system. Furthermore, we have incorporated the third level of mechanics by using the stress intensity range corresponding to the repeated tensile plastic deformation ahead of the crack tip. In the present paper, we shall discuss a more rational integral equation-based formulation in order to integrate the third and fourth levels of micro-mechanics to the first two levels of continuum mechanics. The method is then applied to fatigue crack propagation under the effects of random sequence of clustered loading. As an example of the random sequence of clustered load, we shall use the so-called "storm model". In the crack propagation simulation, we have to take into account of the plastic wake on the crack surfaces, whose thicknesses are influenced by the material parameters involved in the crack growth model. These parameters are first identified by the fatigue tests under combined constant and random loading using a CT specimen. Then, fatigue crack growth is investigated by numerical simulation and fatigue tests for various random sequences of clustered loading. The experimental and numerical results agree quite well with each other, and fatigue crack propagation is found to be considerably retarded under random sequence loading, so that the conventional equivalent stress approach may provide rather conservative results to the real seaway loading. (C) 2011 Elsevier Ltd. All rights reserved.