An isolated system is more restrictive than a closed system as it does not interact with its surroundings in any way. Mass and energy remains constant within the system, and no energy or mass transfer takes place across the boundary. As time passes in an isolated system, internal differences in the system tend to even out and pressures and temperatures tend to equalize, as do density differences. A system in which all equalizing processes have gone practically to completion is considered to be in a state of thermodynamic equilibrium.

Truly isolated physical systems do not exist in reality (except perhaps for the universe as a whole), because, for example, there is always gravity between a system with mass and masses elsewhere. However, real systems may behave nearly as an isolated system for finite (possibly very long) times. The concept of an isolated system can serve as a useful model approximating many real-world situations. It is an acceptable idealization used in constructing mathematical models of certain natural phenomena.

In the attempt to justify the postulate of entropy increase in the second law of thermodynamics, Boltzmann’s H-theorem used equations which assumed a system (for example, a gas) was isolated. That is all the mechanical degrees of freedom could be specified, treating the walls simply as mirror boundary conditions. This inevitably led to Loschmidt's paradox. However, if the stochastic behavior of the molecules in actual walls is considered, along with the randomizing effect of the ambient, background thermal radiation, Boltzmann’s assumption of molecular chaos can be justified.

The second law of thermodynamics is only true for isolated systems. It states that the entropy of an isolated system not in equilibrium will tend to increase over time, approaching maximum value at equilibrium. Overall, in an isolated system, the available energy can never increase, and it complement, entropy, can never decrease. A closed system's entropy can decrease.

It is important to note that isolated systems are not equivalent to closed systems. Closed systems cannot exchange matter with the surroundings, but can exchange energy. Isolated systems can exchange neither matter nor energy with their surroundings, and as such are only theoretical and do not exist in reality (except, possibly, the entire universe).

It is worth noting that 'closed system' is often used in thermodynamics discussions when 'isolated system' would be correct - i.e. there is an assumption that energy does not enter or leave the system.

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