Given a von Neumann algebra M with a faithful normal semi-finite trace τ , we consider the non-commutative Arens algebra L ω (M, τ ) = p 1 L p (M, τ ) and the related algebras L ω 2 (M, τ ) = p 2 L p (M, τ ) and M +L ω 2 (M, τ ) which are proved to be complete metrizable locally convex *-algebras. The main purpose of the present paper is to prove that any derivation of the algebra M + L ω 2 (M, τ ) is inner and all derivations of the algebras L ω (M, τ ) and L ω 2 (M, τ ) are spatial and implemented by elements of M + L ω 2 (M, τ ). In particular we obtain that if the trace τ is finite then any derivation on the noncommutative Arens algebra L ω (M, τ ) is inner.