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Ventral or incisional hernia are a common disease pattern in general surgery. Most commonly, a mesh repair is used for reconstruction, whereby the mesh itself might cause complications, like infections or adhesions. Biological materials, like biocellulose, might reduce these clinical problems substantially. In this prospective rodent study, a biocellulose mesh (produced by Gluconacetobacter xylinus) was implanted either by a sublay technique or as supplementation of the abdominal wall. After an observation period of 90 days, animals were sacrificed. The adhesions after the reconstruction of the abdominal wall were moderate. The histologic investigations revealed that the biocellulose itself was inert, with a minimal regenerative response surrounding the mesh. The explanted mesh showed a minimal shrinkage (around 15%) as well as a minimal loss of tear-out force, which might be without clinical relevance. This is the first in vivo study describing biocellulose as a suitable mesh for the repair of ventral hernia in two different hernia models. The material seems to be a promising option for solving actual problems in modern hernia surgery.