The hydraulic conductivity of a connective tissue is determined both by the fine ultrastructure of the extracellular matrix and the effects of larger particles in the interstitial space. We explored this relationship by examining the effects of 30 or 90 nm diameter latex nanospheres, or low-density lipoproteins (LDL) on the hydraulic conductivity of Matrigel^TM, a basement membrane matrix. The specific hydraulic conductivity (K) of Matrigel^TM with latex nanospheres or LDL particles added at 4.8% weight fraction was measured and compared to that of Matrigel^TM alone. The LDL-derived lipids in the gel were visualized using transmission electron microscopy and were seen to have aggregated into particles up to 500 nm in size. The addition of these materials to the medium markedly decreased K, with the LDL-derived lipids having a much larger effect than did latex nanospheres. Debye-Brinkman theory was used to predict the effect of addition of particles on K of the medium. The theoretical predictions matched well with the results from adding latex nanospheres. However, LDL decreased K more than was predicted by the theory. The validation of the theoretical model for rigid particles embedded in extracellular matrix suggests it could be used to make predictions about the influence of particulates (e.g. collagen, elastin, cells) on hydraulic conductivity of the fine filamentous matrix in connective tissues. In addition, the larger-than-predicted effects of lipids on hydraulic conductivity may magnify pathology associated with lipid accumulation, such as in Bruch's membrane during macular degeneration and the blood vessel wall in atherosclerosis.