Parylene C has been preferred in various microfluidic and packaging applications as a chemical barrier; therefore, its durability in chemicals is critical to maintain functionality of the devices. In this paper, we investigated solvent compatibility of Parylene C in a range of solvents with regard to swelling of it and the change in its surface roughness at room temperature. The results of Parylene C swelling were associated with solubility parameter, δ (cal/cm 3 ) 1/2 , which is predicted from the parameters of dispersion, polar, and hydrogen-bonding forces. Solvents that swelled Parylene C film layer mostly were benzene, chloroform, trichloroethylene, and toluene, while methanol, 2-propanol, ethylene glycol, and water did not cause any swelling. Subsequently, the adverse effects of diffusion of solvents through a Parylene C film layer were demonstrated by stripping of the encapsulated photoresist. In addition, a comparison was made between Parylene C and poly(dimethyl)siloxane (PDMS) considering the data of swelling ratios obtained from the experimental findings and the literature, respectively. Experimental findings showed that Parylene C is much more compatible to solvents than PDMS in high-throughput microfluidic and packaging applications. These results will be of great value to scientists for understanding compatibility of any selected solvent on Parylene C in the applications of micro devices.[2013-0113]