Lipid-based liquid crystalline materials are of increasing interest for use as drug delivery systems. The intricate nanostructure of the reversed bicontinuous cubic (V2) and inverse hexagonal (H2) liquid crystal matrices have been shown to provide diffusion controlled release of actives of varying size and polarity. In this study, we extend the understanding of release to other self-assembled phases, the micellar cubic phase (I2) and inverse micelles (L2). The systems are comparable as they were all prepared from the one lipid, glyceryl monooleate (GMO), which sequentially forms all four phases with increasing hexadecane (HD) content in excess water. Phase identity was confirmed by small angle X-ray scattering (SAXS). SAXS data indicated that four mesophases were formed with increasing HD content at 25 °C: V2 phase (Pn3m space group) formed at 0–4% (w/w) HD, H2 phase formed at 4–25% (w/w) HD, I2 phase (Fd3m space group) formed at 25–40% (w/w) HD and finally L2 phase formed at >40% (w/w) HD. Analogous compositions using phytantriol rather than GMO as the core lipid did not produce the I2 phase, with only V2 to H2 to L2 transitions being apparent with increasing HD concentration. In order to relate the liquid crystal phase structure to drug release rate, in vitro release tests were conducted by incorporating radio-labelled glucose as a model hydrophilic drug into the four GMO-based mesophases. It was found that the drug release followed first-order diffusion kinetics and was fastest from V2 followed by L2, H2, and I2. Drug release was shown to be significantly faster from bicontinuous cubic phase than the other mesophases, indicating that the state of the water compartments, whether open or closed, has a great influence on the rate of drug release. It is envisioned that liquid crystalline mesophases with slower release characteristics will more likely have potential applications as sustained release drug delivery systems, and hence that the bicontinuous cubic phase is not necessarily the best choice for a sustained release matrix.