Aim To explore the molecular mechanisms of the change of whole blood viscoelasticity in the patients with coronary heart disease (CHD) and its clinical significance. Methods Blood lipids, erythrocyte membrane microviscosity (η), sodium pump activity (SPA), relative content of spectrin (SP), erythrocyte deformability parameters (α) and dynamic modulus (G'), dynamic viscosity (η') were measured in 34 CHD with slight coronary atherosclerosis (As), 32 CHD with complicated coronary As and 35 controls. Results Blood lipids, η, G' and η' were significantly higher, but SPA, SP and α were significantly lower in the CHD than those in controls and the changes of these parameters were more obvious along with the development of coronary As. SPA was correlated negatively to η and positively to SP content and α; G' was correlated negatively to α and positively to η'; SP content was positively correlated with α in CHD. Conclusion The increase of whole blood viscoelasticity was closely associated with the increase of blood lipids, η of erythrocyte membrane and the decrease of erythrocyte SPA, SP content and α, and the decreased α and increased viscoelasticity play an important role in the course of coronary As.